Biomedical subjects

N Dafny

Publications and source records attributed to N Dafny.

At least 109 records · Page 6Linked to original sources

PubMed1986

Suppression of the induction of delayed hypersensitivity in rats by repetitive morphine treatments.

Previous in vitro experiments suggest that lymphocyte function may be altered in the presence of opiates. The effect of morphine treatment upon specific T lymphocyte function in vivo was investigated in rats. Following morphine treatment, rats were incapable of responding to immunization with the T-dependent antigens of Mycobacterium bovis, strain BCG. The absence of a delayed hypersensitive skin response to tuberculin in chronic morphine-treated rats supports the hypothesis that opiates may interact with the cells of the immune system. A potential communication between the nervous system and cells of the immune system is proposed.

Animals↗

PubMed1986

Evidence that opiate addiction is in part an immune response. Destruction of the immune system by irradiation-altered opiate withdrawal.

Experiments were performed to determine whether physical dependence on opiates (CNS phenomena) can be altered by destruction of the immune system. Irradiation, prior to or after chronic treatment with morphine significantly reduced the opiate-withdrawal syndrome as assessed by naloxone-induced abstinence. This study supports the proposition that addiction to opiates is related, at least in part, to interaction between the central nervous system (CNS) and the immune system.

Animals↗

PubMed1986

Rat pineal exhibits two electrophysiological patterns of response to microiontophoretic norepinephrine application.

The spontaneous activity of 117 pineal units was recorded in urethane-anesthetized rats. The pineal units exhibited a wide range of firing rates of which 50% were on average slower than 14 spikes per second. Superior cervical ganglion (SCG) stimulation was studied in 76 pineal units; this stimulation caused excitation in 55% of the units. Microiontophoretic application of norepinephrine (NE) induced changes of firing rates in 61% of the pineal units tested. Two patterns of activity following NE microiontophoresis was observed: increase in firing rate (64%) and decrease in firing rate (36%). NE-induced excitation was observed only in those units excited by SCG stimulation. When NE and SCG stimulation were applied together, partial summation of the excitation induced by each one alone was observed. None of the units in which NE depressed the firing rate responded to SCG stimulation. Local application of propranolol blocked the excitation initiated by SCG stimulation as well as the excitation and the depression induced by NE microiontophoresis.

Action Potentials↗

PubMed1985

Cyclosporine alters opiate withdrawal in rodents.

Opiates exert numerous effects on all levels of the central nervous system with tolerance, physical dependence and withdrawal being characteristics of this drug class. The degree of dependence is directly correlated to the intensity of withdrawal. Therefore, success in modifying the withdrawal syndrome may shed light on the dynamics of opiate addiction. The present study demonstrates that cyclosporine, a widely used immunosuppressive drug, considerably modified the behavioral signs of a naloxone-induced abstinence syndrome in morphine-addicted rats. In previous experiments, alpha-interferon has shown similar results. The similarity in actions of these two immunomodulator drugs is discussed and we suggest that opiate addiction may involve the immune system.

Animals↗

PubMed1985

Interaction of norepinephrine and superior cervical ganglion input in the rat pineal body.

The effects of superior cervical ganglion stimulation and the local application of norepinephrine or its antagonist propranolol were studied in 18 pineal cells. In 61% of the pineal cells, stimulation elicited excitation; the same cells also responded by excitation to norepinephrine ejection. When stimulation and norepinephrine ejection were applied together, summation (of the excitation) was observed in these cells. Several cells that failed to respond to stimulation did respond to norepinephrine ejection, but with the opposite pattern, i.e., decrease of firing rates. Propranolol prevented the norepinephrine-induced excitation and inhibition, as well as the excitation produced by stimulation. We suggest that norepinephrine regulates pineal activity by two routes: activation of the sympathetic neuronal input and inhibition by way of the circulation.

Animals↗

PubMed1985

Prolonged daily inhalation of halothane modifies the dose-response pattern to acute administration of halothane. An electrophysiological study.

Sensory-evoked field potentials were obtained from freely moving rats implanted sterotaxically with permanent electrodes in the parafasciculus thalami (PF), mesencephalic central gray (CG), ventromedial hypothalamus (VMH) and somatosensory cortex (SCX). Animals were exposed to chronic, subanesthetic inhalation of halothane (0.5%, 3 hr/day, 5 days/week) for 56 days. The averaged acoustic evoked responses (AAER) were recorded on day 0, as well as at 28 and 56 days after a 48-hr halothane-free period ("control") and after acute doses of halothane (0.25, 0.5 and 1.5%). In general, the averaged sensory-evoked responses from each structure were affected at day 0 of the experiment in dose-response manner, and suppression of the responses was the main effect of halothane. Chronic exposure to subanesthetic inhalation of halothane produced marked alteration of the "control" recording from 3 CNS structures; mainly from the mesencephalic central gray, the parafasciculus thalami and the somatosensory cortex and the direction (increase or decrease) of the averaged acoustic evoked responses in all the four CNS sites studied. The total responsiveness was modified as well, i.e. the recordings obtained from the mesencephalic central gray and somatosensory cortex exhibited hypersensitivity while the recordings obtained from the parafasciculus thalami and ventromedial hypothalamus exhibited tolerance. It is concluded that prolonged and intermittent inhalation of halothane can alter the electrophysiological properties of the four structures investigated.

Acoustic Stimulation↗

PubMed1985

Three different types of alpha-interferons alter naloxone-induced abstinence in morphine-addicted rats.

The opiate abstinence syndrome represents a fundamental feature of the addictive process, with the degree of addiction being directly correlated to the intensity of withdrawal. Therefore, the discovery of substances capable of attenuating withdrawal signs may provide insights into the dynamics of opiate addiction. The present study demonstrates that three different types of alpha-interferons modify the behavioral signs associated with naloxone-induced abstinence in rats addicted to morphine. These observations suggest that opiate addiction may, in part, be due to an immune response in that immunomodulators (interferon) are capable of altering the naloxone-induced abstinence syndrome in morphine-dependent rats.

Animals↗

PubMed1985

Does the immune system communicate with the central nervous system? Interferon modifies central nervous activity.

The present investigation determined whether an immunomodulator agent modified the central nervous system activity as measured behaviorally and neurophysiologically. Two types of interferons (IFNs), alpha (alpha) and gamma (gamma), were applied locally (microiontophoretically) into various regions of the rat brain simultaneously with single neuron recording from the cerebral cortex, hippocampus, thalamus and hypothalamus. Of the various IFNs, only alpha-IFN altered single cell activity in all brain structures in a dose-dependent manner. Moreover, systemic administration of alpha-IFN altered the naloxone-induced abstinence syndrome in morphine-dependent rats. These observations suggest that immunomodulators such as alpha-IFN are capable of influencing directly central nervous system function as well as the immune system.

Animals↗

PubMed1985

Dose effects of halothane on sensory evoked responses obtained from the cortex, reticular formation and central gray.

Sensory evoked field potentials were recorded from the mesencephalic reticular formation (MRF), central gray (CG) and somatosensory cortex (SCX), following incremental doses of halothane in freely-moving rats. Halothane concentrations of 0.25%, 0.5% 1.0% and 2.0% were used. In general, the responses from each structure were affected in dose response manner. The averaged acoustic evoked responses (AAER) exhibit more sensitivity to halothane than the averaged visual evoked responses (AVER). The evoked response and its components obtained from each structure were affected differently by halothane mainly following the initial two halothane doses, (0.25% and 0.5%); mainly increase in amplitude was observed in the recording obtained from the MRF, decrease in the CG, and mixed (increase and/or decrease) in SCX. The degree of the depression of the sensory evoked responses was directly correlated to the level of anesthesia as assessed by sural nerve stimulation.

Animals↗

PubMed1985

Interferon as an endocoids candidate preventing and attenuating opiate addiction.

Morphine exert numerous effects of all levels of the central nervous system with tolerance, physical dependence and withdrawal being characteristic of this drug class. The degree of dependence is directly correlated to the intensity of withdrawal, success in modifying the withdrawal syndrome may shed light on the dynamic of morphine addiction. The present study demonstrated that alpha-interferon (IFN) significantly modifies the naloxone-induced abstinence syndrome in morphine dependent rats. Single cortical neurons recording and microiontophoretic application of IFN, morphine and naloxone failed to support existing hypothesis that IFN effects are mediated through opiate receptors. Since IFN's are widely present in animals bodies, including the brain, and are locally synthesized. Our observation suggests that IFN's are endocoids which serve to prevent tolerance and dependence to endogenous peptides.

Animals↗

PubMed1984

Morphine effects on spontaneous, nociceptive, antinociceptive and sensory evoked responses of parafasciculus thalami units in morphine naive and morphine dependent rats.

The present experiments used freely behaving animals previously implanted with permanent recording electrodes within the parafasciculus thalami (PF) and stimulation electrodes in nociceptive and antinociceptive areas. The spontaneous and the evoked activity in PF neurons following nociceptive, antinociceptive and sensory stimulation, as well as the effects of morphine and its antagonist naloxone on these inputs in morphine naive and morphine dependent animals, were investigated. The observations demonstrated that the spontaneous activity of PF neurons exhibits variable spontaneous firing rates which are affected by acute and chronic morphine treatment. The PF neuronal population exhibits neurophysiological activity characteristic of morphine dependence, tolerance and withdrawal from morphine. The PF receives mono-, oligo- and polysynaptic inputs from multiple sources, including regions associated with pain pathways which converge on PF cells, as well as from sites involved in pain suppression mechanisms, which supports the hypothesis of a role of the PF as a modulator of pain input. The nociceptive, antinociceptive and sensory inputs are not modified by chronic morphine treatment, but single doses of morphine have remarkable effects on those inputs in morphine naive and morphine dependent animals; naloxone reversed the morphine effects on the evoked activity.

Action Potentials↗

PubMed1984

Does interferon exert its actions through opiate receptors.

It had been reported that alpha interferon (alpha-IFN) induces endorphin-like effects such as analgesia and catatonia. These effects, reversed and prevented by naloxone, suggest that the alpha-IFN effect is mediated via opiate receptors. In order to examine this hypothesis, the present study was initiated. Extracellular cortical cell recording and microiontophoretic application of alpha-IFN, morphine, and naloxone, as well as the application of these three drugs on the coaxially stimulated guinea-pig ileum preparation were used. alpha-IFN application induced excitation in cortical cells and on the guinea-pig ileum. In contrast, the main effect elicited by morphine was a decrease in both preparations. Naloxone was able to reverse and/or prevent the morphine effects in both preparations, but failed to alter the effects induced by alpha-IFN. The present observations using the guinea-pig ileum preparation and cortical neurons recording failed to support the hypothesis that alpha-IFN effects are mediated via opiate receptors.

Animals↗

PubMed1984

Microiontophoretic application of morphine and naloxone to neurons in hypothalamus of rat.

The present experiments used urethane-anesthetized rats and single cell recording to study the electrophysiological properties of ventromedial hypothalamic (VMH) cells following different doses of morphine and naloxone, applied microiontophoretically. More than 45% of ventromedial hypothalamic units reacted in a dose-response fashion to local application of morphine. In the majority of the ventromedial hypothalamic neurons, naloxone failed to reverse the effects of morphine. Naloxone alone had effects on 37% of the ventromedial hypothalamic units. The ventromedial hypothalamic units exhibited different response patterns from those observed from other CNS sites in response to the microiontophoretic application of morphine and naloxone; this difference is discussed. The present neurophysiological findings support the existence of opiate target sites with multiple opiate receptors within the ventromedial hypothalamus.

Animals↗

PubMed1984

Effects of morphine on: spontaneous, dorsal raphe, spinal tract of trigeminal nucleus, medial lemniscus and reticular lateral magnocellular evoked responses of hypothalamic units, in naive and morphine physically dependent rats.

The spontaneous activity and the inputs to the medial basal hypothalamus (MBH) following dorsal raphe (DR), spinal tract of the trigeminal nerve (SpV), medial lemniscus (ML), reticular lateral magnocellular nucleus ( RLM ) and acoustic (Ac) stimulation and the effects of morphine and the opioid antagonist, naloxone, on these inputs, were investigated in morphine-naive and morphine-dependent animals. The observations were obtained in freely behaving animals previously implanted with permanent electrodes. The spontaneous activity of MBH neurons exhibits heterogenic spontaneous firing rates. This spontaneous activity is affected by acute and chronic morphine treatment. The MBH neuronal population exhibits neurophysiological patterns of tolerance of morphine dependence and withdrawal. The central input exerts a marked influence on MBH neurons in both naive and morphine-dependent animals. These inputs are modified by morphine challenge dose in both preparations, i.e., in morphine-naive and morphine-dependent animals, and are reversed by naloxone. The DR and Ac inputs affect the MBH neuronal activity differently from that observed following SpV, ML and RLM stimuli. The effects of morphine and naloxone on the DR and Ac input in morphine-naive and morphine-dependent animals differ from those observed following SpV, ML and RLM inputs. The MBH neurons exhibited a high percentage of convergence to Ac, DR, SpV, ML and RLM stimulation.

Acoustic Stimulation↗

PubMed1984

Alpha and gamma interferons' effects on cortical and hippocampal neurons: microiontophoretic application and single cell recording.

Responses of 96 extracellular spontaneous active cortical and hippocampal neurons to microiontophoretically applied four types of alpha interferons (alpha-IFNs), one type of gamma interferon (gamma-IFN) as well as three fractions of gamma-IFNs were examined. All four types of alpha-IFN ejections increased the discharge of the majority of neuron tested. Significant differences of the number of cells excited and the intensity of the excitation among the 4 types of alpha-IFN were observed. The most significant effects were induced by Cantell's human leukocyte alpha-IFN followed by the Hoffman-LaRoche recombinant alpha-IFN which exhibited a dose dependent effect (i.e., each higher dose of IFN affected more neurons and intensified the excitation) on the hippocampal and cortical cells respectively. Neither the IFN carrier (albumin), nor the gamma-IFNs and its fractions, as well as current ejection, altered the extracellular spontaneous active of these 96 cortical and hippocampal neurons respectively. These observations show that the immunomodulator alpha-IFNs, but not gamma-IFNs, exerts excitatory effects on neuronal activity recorded from these two brain structures and support the view that the brain is capable of communicating with the immune system.

Action Potentials↗

PubMed1984

Interferon: a candidate as the endogenous substance preventing tolerance and dependence to brain opioids.

It has been suggested that protein synthesis and immunological factors play a role in the development of tolerance and dependence to opiates. Interferon (IFN) is known to influence protein synthesis and the immune system. Our and other data suggest that IFN may be an agent that prevents the development of tolerance and the physical dependence to endogenous opioids.

Adrenocorticotropic Hormone↗

PubMed1984

Microiontophoretically applied morphine and naloxone on single cell activity in the parafasciculus nucleus of naive and morphine-dependent rats.

Responses of parafasciculus (PF) thalamic neurons to microiontophoretically applied morphine and naloxone were examined in morphine-naive and morphine-dependent rats. The PF neurons exhibited high responsiveness (65%) to microiontophoretically applied morphine. Five different patterns of response to morphine in naive animals were obtained from the PF neurons. In morphine-dependent rats, the total responsiveness to microiontophoretic application of morphine was reduced dramatically (to 30%) and the response patterns to morphine were significantly (P less than .01) altered; this indicates that the PF neurons exhibit tolerance to morphine. Naloxone applied together with morphine only blocked the morphine-induced decreases in firing rates, but not the increases to which naloxone exhibited opiate agonist effects. Microiontophoretic application of naloxone alone, before morphine ejections in morphine-naive rats, induced changes in 51% of the PF neuronal population studied. Most of them (73%) responded with decreased firing rates. In morphine-dependent rats, more units responded to naloxone ejection (64%) as compared with the morphine-naive group. Excitation was the dominant response (73%) to naloxone treatment. The application of naloxone alone in naive and morphine-dependent rats demonstrated that the PF units responded in a characteristic dose-response manner to incremental naloxone administration. The present observations support our previous experiments using systemic applications of morphine and naloxone in freely behaving animals.

Animals↗

PubMed1983

An ascending serotonergic pain modulation pathway from the dorsal raphe nucleus to the parafascicularis nucleus of the thalamus.

Three types of spontaneously active neurons were found in the parafascicularis (PF) nucleus of the thalamus of the rat: slow firing units (0.5-10 spikes/s), bursting units (2-5 spikes/burst in 10-20 ms, one burst every 1-2 s) and fast firing units (15-40 spikes/s). A similar population of neurons was found in the PF of rats treated with 5,7-dihydroxytryptamine (5,7-DHT), a serotonin neurotoxin. Noxious tail pinch (TP) caused 68% of the PF neurons to increase their firing rates to 242% of their initial baseline activity, while non-noxious touch stimulation failed to induce a response. In the 5,7-DHT-treated rats, TP caused 85% of the neurons in the PF to increase their firing rates to 581% of their initial baseline activity and 22% of the neurons increased their firing in response to touching the tail. Both the number of cells responding (P less than 0.05) and the percentage increase (P less than 0.001) were statistically greater in serotonin-depleted rats than in controls. This indicates that serotonin (5-HT) has a tonic inhibitory influence on responses to both noxious and non-noxious sensory stimuli. In control rats, electrical stimulation of the dorsal raphe nucleus (DR) decreased the firing rates of PF neurons. In contrast, the same DR stimulation induced an increase in PF firing rates during stimulation in serotonin-depleted rats and this increase in firing rates remained several seconds after cessation of stimulation. This indicates that the DR may use at least two different neurotransmitters in its projections to forebrain structures. In control rats, the TP stimulation induced an increase in firing rates of rates of PF neurons while DR stimulation attenuated the excitation induced by TP stimulation. In serotonin-depleted rats, DR stimulation and TP both caused an increase in firing rates. This effect was not additive indicating that there may be a serotonergic projection from the DR to the PF which modifies responses to somatosensory stimuli. The inhibitory effects elicited by electrical stimulation were limited to the immediate area of the DR. Stimulation of the adjacent reticular formation 1 mm lateral to the DR produced the opposite effect, an increase in firing rate often accompanied by driven spike activity in the PF.

Animals↗